2-(Chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one → 2-((4-(2-Hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-6-methyl thieno[2,3-d]pyrimidin-4(3H)-one

HRID 1091688Notes

Reaction equation

HRID 1091688 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[C:7]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:6][NH:5][N:4]=1.CC(C)([O-])C.[K+].Cl[CH2:21][C:22]1[NH:23][C:24](=[O:32])[C:25]2[CH:30]=[C:29]([CH3:31])[S:28][C:26]=2[N:27]=1>C1COCC1>[OH:11][C:8]([C:7]1[C:3]([C:2]([F:1])([F:12])[F:13])=[N:4][N:5]([CH2:21][C:22]2[NH:23][C:24](=[O:32])[C:25]3[CH:30]=[C:29]([CH3:31])[S:28][C:26]=3[N:27]=2)[CH:6]=1)([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 64916832-(Chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-oneHCID 23665647Potassium tert-butoxideHCID 178458810HCID 178458810, compound

Product 1

HCID 665916902-((4-(2-Hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-6-methyl thieno[2,3-d]pyrimidin-4(3H)-oneYield 4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)propan-2-ol (73 mg, 0.376 mmol) and potassium tert-butoxide (127 mg, 1.13 mmol) in THF (2 mL) was stirred for ˜2 min. To this was added 2-(chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one (81 mg, 0.376 mmol) and the resultant mixture was stirred for 18 h. The reaction mixture was quenched with saturated NH4Cl solution and concentrated in vacuo. The residue was partitioned between DCM and water and the organic layer was separated. The aqueous layer was extracted with further DCM and the combined organics were washed with saturated brine, dried over MgSO4, filtered and concentrated in vacuo to give a light yellow gum. The gum was purified by preparative LCMS to give the product as a white solid (5 mg, 0.014 mmol, 4%).

Workup

  1. customThe reaction mixture was quenched with saturated NH4Cl solution
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between DCM and water
  4. customthe organic layer was separated
  5. extractionThe aqueous layer was extracted with further DCM
  6. washthe combined organics were washed with saturated brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a light yellow gum
  11. customThe gum was purified by preparative LCMS

Sources & evidence

ORD record
ord-9b52bf88e9314f129e87b4f8ace20b5f
Source dataset
uspto-grants-2012_03
Patent number
US08129397B2

Reaction notes

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